TNF-alpha signaling in glaucomatous neurodegeneration.
Growing evidence supports the role of tumor necrosis factor-alpha (TNF-alpha) as a mediator of neurodegeneration in glaucoma. Glial production of TNF-alpha is increased, and its death receptor is upregulated on retinal ganglion cells (RGCs) and optic nerve axons in glaucomatous eyes. This multifunctional cytokine can induce RGC death through receptor-mediated caspase activation, mitochondrial dysfunction, and oxidative stress. In addition to direct neurotoxicity, potential interplay of TNF-alpha signaling with other cellular events associated with glaucomatous neurodegeneration may also contribute to spreading neuronal damage by secondary degeneration. Opposing these cell death-promoting signals, binding of TNF receptors can also trigger the activation of survival signals. A critical balance between a variety of intracellular signaling pathways determines the predominant in vivo bioactivity of TNF-alpha as best exemplified by differential responses of RGCs and glia. This review focuses on the present evidence supporting the involvement of TNF-alpha signaling in glaucomatous neurodegeneration and possible treatment targets to provide neuroprotection.
Tezel
Gülgün
G
Department of Ophthalmology & Visual Sciences, University of Louisville School of Medicine, Louisville, KY, USA. gulgun.tezel@louisville.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018696:Neuroprotective Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases